6RAB

Ruminococcus gnavus sialic acid aldolase Wild Type

6RAB の概要

• エントリーDOI: 10.2210/pdb6rab/pdb
• 分子名称: Putative N-acetylneuraminate lyase (2 entities in total)
• 機能のキーワード: neu5ac, sialic acid, aldolase, lyase, ruminococcus gnavus
• 由来する生物種: Ruminococcus gnavus ATCC 29149
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74323.31

構造登録者

Owen, C.D.,Bell, A.,Juge, N.,Walsh, M.A. (登録日: 2019-04-05, 公開日: 2019-09-25, 最終更新日: 2024-05-15)

主引用文献

Bell, A.,Brunt, J.,Crost, E.,Vaux, L.,Nepravishta, R.,Owen, C.D.,Latousakis, D.,Xiao, A.,Li, W.,Chen, X.,Walsh, M.A.,Claesen, J.,Angulo, J.,Thomas, G.H.,Juge, N.
Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut.
Nat Microbiol, 4:2393-2404, 2019

PubMed Abstract: Sialic acid (N-acetylneuraminic acid (Neu5Ac)) is commonly found in the terminal location of colonic mucin glycans where it is a much-coveted nutrient for gut bacteria, including Ruminococcus gnavus. R. gnavus is part of the healthy gut microbiota in humans, but it is disproportionately represented in diseases. There is therefore a need to understand the molecular mechanisms that underpin the adaptation of R. gnavus to the gut. Previous in vitro research has demonstrated that the mucin-glycan-foraging strategy of R. gnavus is strain dependent and is associated with the expression of an intramolecular trans-sialidase, which releases 2,7-anhydro-Neu5Ac, rather than Neu5Ac, from mucins. Here, we unravelled the metabolism pathway of 2,7-anhydro-Neu5Ac in R. gnavus that is underpinned by the exquisite specificity of the sialic transporter for 2,7-anhydro-Neu5Ac and by the action of an oxidoreductase that converts 2,7-anhydro-Neu5Ac into Neu5Ac, which then becomes a substrate of a Neu5Ac-specific aldolase. Having generated an R. gnavus nan-cluster deletion mutant that lost the ability to grow on sialylated substrates, we showed that-in gnotobiotic mice colonized with R. gnavus wild-type (WT) and mutant strains-the fitness of the nan mutant was significantly impaired, with a reduced ability to colonize the mucus layer. Overall, we revealed a unique sialic acid pathway in bacteria that has important implications for the spatial adaptation of mucin-foraging gut symbionts in health and disease.

PubMed: 31636419
DOI: 10.1038/s41564-019-0590-7

実験手法

X-RAY DIFFRACTION (1.96 Å)